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169 lines
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<title>06 February, 2024</title>
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<title>Covid-19 Sentry</title><meta content="width=device-width, initial-scale=1.0" name="viewport"/><link href="styles/simple.css" rel="stylesheet"/><link href="../styles/simple.css" rel="stylesheet"/><link href="https://unpkg.com/aos@2.3.1/dist/aos.css" rel="stylesheet"/><script src="https://unpkg.com/aos@2.3.1/dist/aos.js"></script></head>
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<h1 data-aos="fade-down" id="covid-19-sentry">Covid-19 Sentry</h1>
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<h1 data-aos="fade-right" data-aos-anchor-placement="top-bottom" id="contents">Contents</h1>
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<ul>
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<li><a href="#from-preprints">From Preprints</a></li>
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<li><a href="#from-clinical-trials">From Clinical Trials</a></li>
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<li><a href="#from-pubmed">From PubMed</a></li>
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<li><a href="#from-patent-search">From Patent Search</a></li>
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</ul>
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<h1 data-aos="fade-right" id="from-preprints">From Preprints</h1>
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<li><strong>XBB.1.5 monovalent booster improves antibody binding and neutralization against emerging SARS-CoV-2 Omicron variants</strong> -
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<div>
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The rapid emergence of divergent SARS-CoV-2 variants has led to an update of the COVID-19 booster vaccine to a monovalent version containing the XBB.1.5 spike. To determine the neutralization breadth following booster immunization, we collected blood samples from 24 individuals pre- and post-XBB.1.5 mRNA booster vaccination (~1 month). The XBB.1.5 booster improved both neutralizing activity against the ancestral SARS-CoV-2 strain (WA1) and the circulating Omicron variants, including EG.5.1, HK.3, HV.1, XBB.1.5 and JN.1. Relative to the pre-boost titers, the XBB.1.5 monovalent booster induced greater total IgG and IgG subclass binding, particular IgG4, to the XBB.1.5 spike as compared to the WA1 spike. We evaluated antigen-specific memory B cells (MBCs) using either spike or receptor binding domain (RBD) probes and found that the monovalent booster largely increases non-RBD cross-reactive MBCs. These data suggest that the XBB.1.5 monovalent booster induces cross-reactive antibodies that neutralize XBB.1.5 and related Omicron variants.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.03.578771v1" target="_blank">XBB.1.5 monovalent booster improves antibody binding and neutralization against emerging SARS-CoV-2 Omicron variants</a>
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</div></li>
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<li><strong>DNA Prime-Protein Boost Targeting Conformational Non-RBD Region for Broad Cross-Neutralization</strong> -
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<div>
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The preservation of antigen spatial conformation is crucial for inducing the high-quality neutralizing responses. Although the receptor-binding domain (RBD) antigen in SARS-CoV-2 vaccines shows satisfactory conformation preservation, it remains susceptible to the immune escape. Therefore, exploring conformational epitopes beyond the RBD region to achieve cross-neutralization becomes an attractive topic. In this study, we used a DNA prime-protein boost regimen to obtain potent humoral responses. Further analysis revealed that boosting antibody responses targeting conformational non-RBD region is crucial for enhancing cross-neutralization against the Wuhan-01, Delta and Omicron subvariants. Via analyzing the distribution of conformational epitopes, and quantifying epitope-specific binding antibodies, we verified a positive correlation between the proportion of binding antibodies against the N-terminal domain (NTD) supersite (a conformational non-RBD epitope) and SARS-CoV-2 neutralization potency. The current work highlights the importance of conformational non-RBD-specific binding antibodies in mediating viral cross-neutralization and provides a new insight in overcoming the immune escape of SARS-CoV-2 variants.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.04.578544v1" target="_blank">DNA Prime-Protein Boost Targeting Conformational Non-RBD Region for Broad Cross-Neutralization</a>
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</div></li>
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<li><strong>The accomplices: Heparan sulfates and N-glycans foster SARS-CoV-2 spike:ACE2 receptor binding and virus priming</strong> -
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<div>
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The SARS-CoV-2 spike glycoprotein mediates virus attachment to human host cells by binding angiotensin-converting enzyme 2 (ACE2) and heparan sulfate (HS) proteoglycans. To elucidate the structure, dynamics, and functional consequences of these interactions, we carried out microsecond-long all-atom molecular dynamics simulations, followed by random acceleration molecular dynamics simulations, of the fully glycosylated spike:ACE2 complex with and without heparin chains bound. We find that heparin, a model for HS, promotes structural and energetic stabilization of the active conformation of the spike receptor binding domain (RBD) and reorientation of ACE2 toward the N-terminal domain in the same spike subunit as the RBD. Spike and ACE2 N-glycans exert synergistic effects, promoting better packing, strengthening the protein:protein interaction, and prolonging the residence time of the complex. ACE2 and heparin binding trigger rearrangement of the S2' functional site through allosteric interdomain communication. HS thus has a multifaceted role in facilitating SARS- CoV-2 infection.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.05.578888v1" target="_blank">The accomplices: Heparan sulfates and N-glycans foster SARS-CoV-2 spike:ACE2 receptor binding and virus priming</a>
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</div></li>
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<li><strong>Who Can I Count On: Honor, Self-Reliance, and Family in the United States and Iran</strong> -
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<div>
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People in honor cultures take measures to uphold their reputations. However, it is unclear how aspects of honor vary between societies. Here, we explore the tension between competing views about honor – honor as self-defense narrowly defined in terms of self-reliant tendencies vs. honor broadly defined by demonstrations of strength and virtue. The former suggests that self-reliance, in demonstrating the ability of the individual to defend themself, is a crucial component of honor, while the latter allows the importance of self-reliance in honor to vary depending on moral and cultural factors. To examine these implications, we conducted studies in the U.S., where self-reliance is virtuous, and in Iran, where individual agency must be balanced against the interests of kin. Americans (Studies 1, 2; n = 978) who endorsed honor values tended to ignore governmental COVID-19 measures because they preferred relying on themselves. In contrast, honor-minded Iranians (Study 3; n = 201) adhered to public-health guidelines and did not prefer self-reliance. Moreover, honor-minded Iranians endorsed family-reliance, but did not moralize self-reliance (Study 4; n = 107), while honor-minded Americans endorsed family-reliance and moralized self-reliance (Study 4; n = 120). Results suggest that local norms may shape how honor is expressed across cultures.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/h26pt/" target="_blank">Who Can I Count On: Honor, Self-Reliance, and Family in the United States and Iran</a>
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</div></li>
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<li><strong>Examining enduring effects of COVID-19 on college students’ internalizing and externalizing problems: A four-year longitudinal analysis</strong> -
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<div>
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The current study sets out to examine the extent to which college students’ trajectories of mental health symptoms (depression, social anxiety, impulsivity, and aggression) and problematic alcohol use changed as the COVID-19 pandemic progressed; we hypothesize increases in all levels and slopes of all outcomes over time following the pandemic’s onset. We also hypothesize greater mental health symptoms and problematic alcohol use (i.e., higher levels of and increases in outcomes over time) following COVID-19 among individuals who experienced higher levels of loneliness, financial strain, and health anxiety at the time of the pandemic’s onset.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/6c8y2/" target="_blank">Examining enduring effects of COVID-19 on college students’ internalizing and externalizing problems: A four-year longitudinal analysis</a>
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</div></li>
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<li><strong>Rapid worldwide return to nature after lockdown as a motivator for conservation and sustainable action</strong> -
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<div>
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Exposure to nature is increasingly regarded as a key part of human health, and the recognition that urban environments must provide access to green spaces for the wellbeing of citizens. The beginning of the COVID-19 pandemic in 2020 led to many governments issuing stay-at-home orders and closing parks, limiting the options of accessible green spaces for people seeking to safely socialise and cope with stress. Here, we gain a global perspective on how quickly people returned to nature (visiting parks and beaches) in comparison to necessities (accessing groceries and pharmaceuticals) and luxury activities (retail purchases and recreation) following COVID-19 lockdowns using Google Mobility data. We found that people from around the world returned to nature 76 days after peak lockdown, 28 days after people returned to necessities and 77 days before the return to luxuries. Central Asia, Europe, and Northern America returned to nature before necessities. These patterns held even after seasonally-detrending the data. We further found a strong negative correlation between the speed people pulsed back to nature and the strength of government response measures. ¬Combined, our data support the value of nature to people and the need to consider access to green and natural space for human well-being. At the same time, the large-scale return to nature also highlighted the need to promote messages on how to minimise the impacts of human activities in these spaces. We advocate for building and protecting green spaces, combined with strong eco-education, to foster pro-environmental behaviour.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/socarxiv/2ghu3/" target="_blank">Rapid worldwide return to nature after lockdown as a motivator for conservation and sustainable action</a>
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</div></li>
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<li><strong>Emotions in misinformation studies: Distinguishing affective state from emotional response and misinformation recognition from acceptance</strong> -
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<div>
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Emotions play a crucial role in information processing. Prior studies indicate that high-arousal emotions may elicit rapid, intuitive thinking, tricking people into judging misinformation as truthful. Yet, few studies have distinguished prior affective state from emotional reactions to false news, both of which may influence belief in falsehoods in different ways. Replicating and extending Martel et al. (2020), we conducted a pre-registered online survey in Austria (N = 422), investigating associations of emotions and discernment of false and real news related to COVID-19. We found no associations of affective state with discernment, but different emotional responses to false and real news — namely, more anger and less joy for false news. A curvilinear relationship of anger with discernment showed that both participants who were good and bad at discerning real from false news responded with anger. The automated analysis of 5,613 open-ended textual responses suggested that anger may have arisen for different reasons in these different groups. It seemed to also arise when people recognized the false news as such, not only when people accepted it. We conclude that studies need to distinguish between prior affective state and emotional response to misinformation and consider individuals’ prior beliefs as determinants of emotions.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/udqms/" target="_blank">Emotions in misinformation studies: Distinguishing affective state from emotional response and misinformation recognition from acceptance</a>
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</div></li>
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<li><strong>Sex-Specific Development of ssRNA Virus Receptor Gene Expression in the Human Brain</strong> -
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<div>
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Background: The COVID-19 pandemic has focused research on the detrimental impact of neuroinvasive single-strand RNA (ssRNA) viruses. Those viruses cause a wide range of human diseases ranging from mild to severe life-threatening conditions, and host factors such as age, sex, and the expression of virus receptors can influence the severity of the infection. For example, older adults and males have a bias for severe disease with COVID-19 infection, but females have a higher risk of Long-COVID. However, there is a gap in understanding the expression of receptors for ssRNA viruses in the human brain and how that expression varies by age and sex. Here, we studied the expression of ssRNA virus receptors in the human brain and compared lifespan changes in females and males to identify age- and sex-specific developmental patterns. Methods: We used a publicly available transcriptomic database of human brain development to characterize the development of 67 viral host factor genes for 10 ssRNA virus families. A data-driven approach was applied to characterize the lifespan trajectories for those ssRNA receptors using samples from 15 brain areas (n=700, F=306, M=394, age range:4 mo-82 yrs). Then, high-dimensional trajectory analyses and visualizations, including tSNE, were used to compare lifespan changes for females and males among the 15 brain areas. Results: Unsupervised hierarchical clustering of the 2010 trajectories identified 25 different patterns with a range of sex bias from ones with only female data to ones with only male data. Differential Expression Sliding Window Analysis (DE-SWAN) found a brain-wide pattern of virus receptor sex differences in childhood, before puberty. The virus families had a range of sexual dimorphism, with the Pneumoveridae family being the most dimorphic. Finally, high dimensional visualization of ssRNA virus receptor development in the 15 brain areas showed that the cortex is distinct for females and males. Conclusions: Females are often described as developing precociously relative to males, but our findings paint a different picture. Instead, we found that sex differences in virus receptor development in the human brain do not reflect simply linear shifts and are best described as females and males following distinct high-dimensional trajectories.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.10.11.561925v2" target="_blank">Sex-Specific Development of ssRNA Virus Receptor Gene Expression in the Human Brain</a>
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</div></li>
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<li><strong>How Does The COVID-19 Pandemic Impact on Population Mental Health? A Network Analysis of COVID Influences On Depression, Anxiety and Traumatic Stress in the UK Population</strong> -
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<div>
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Background. The COVID-19 emergency has led to numerous attempts to assess the impact of the pandemic on population mental health. Findings indicate an increase in depression and anxiety but have been limited by the lack of specificity about which aspects of the pandemic (e.g. viral exposure or economic threats) have led to adverse mental health outcomes. Methods. Network analyses were conducted on data from wave 1 (N = 2025 recruited March 23rd – March 28th 2020) and wave 2 (N = 1406 recontacts, 22 April – 1 May 2020) of the COVID-19 Psychological Research Consortium Study, an online longitudinal survey of a representative sample of the UK adult population. Our models included depression (PHQ-9), generalised anxiety (GAD-7) and trauma symptoms (ITQ) and also measures of Covid-specific anxiety, exposure to the virus in self and close others as well as economic loss due to the pandemic. Results. A mixed graphical model at wave 1 indicated that economic adversity impacted on anxiety symptoms via specific anxiety about the pandemic. There was no association between viral exposure and symptoms. Ising network models using clinical cut-offs for symptom scores at each wave yielded similar findings with the exception of a modest effect of viral exposure on trauma symptoms at wave 1 only. Anxiety and depression symptoms formed separate clusters at wave 1 but not wave 2. Conclusions. The psychological impact of the pandemic evolved in the early phase of lockdown. Adverse psychiatric outcomes were particularly associated with exposure to the economic consequences of the pandemic.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/preprints/psyarxiv/8xtdr/" target="_blank">How Does The COVID-19 Pandemic Impact on Population Mental Health? A Network Analysis of COVID Influences On Depression, Anxiety and Traumatic Stress in the UK Population</a>
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<li><strong>Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses</strong> -
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<div>
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Some respiratory viruses can cause a viral interference through the activation of the interferon (IFN) pathway that reduces the replication of another virus. Epidemiological studies of coinfections between SARS-CoV-2 and other respiratory viruses have been hampered by non-pharmaceutical measures applied to mitigate the spread of SARS-CoV-2 during the COVID-19 pandemic. With the ease of these interventions, SARS-CoV-2 and influenza A viruses can now co-circulate. It is thus of prime importance to characterize their interactions. In this work, we investigated viral interference effects between an Omicron variant and a contemporary influenza A/H3N2 strain, in comparison with an ancestral SARS-CoV-2 strain and the 2009 pandemic influenza A/H1N1 virus. We infected nasal human airway epitheliums with SARS-CoV-2 and influenza, either simultaneously or 24 h apart. Viral load was measured by RT-qPCR and IFN-/{beta}/{lambda}1/{lambda}2 proteins were quantified by immunoassay. Expression of four interferon-stimulated genes (ISGs; OAS1/IFITM3/ISG15/MxA) was also measured by RT-droplet digital PCR. Additionally, susceptibility of each virus to IFN-/{beta}/{lambda}2 recombinant proteins was determined. Our results showed that influenza A, and especially A/H3N2, interfered with both SARS-CoV-2 viruses, but that SARS-CoV-2 only interfered with A/H1N1. Consistently with these results, influenza, and particularly the A/H3N2 strain, caused a higher production of IFN proteins and expression of ISGs than SARS-CoV-2. The IFN production induced by SARS-CoV-2 was marginal and its presence during coinfections with influenza was associated with a reduced IFN response. All viruses were susceptible to exogenous IFNs, with the ancestral SARS-CoV-2 and Omicron being less susceptible to type I and type III IFNs, respectively. Thus, influenza A causes a viral interference towards SARS-CoV-2 most likely through an IFN response. The opposite is not necessarily true, and a concurrent infection with both viruses leads to a lower IFN response. Taken together, these results help us to understand how SARS-CoV-2 interacts with another major respiratory pathogen.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.02.578538v1" target="_blank">Viral interference between severe acute respiratory syndrome coronavirus 2 and influenza A viruses</a>
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<li><strong>Development of a cell-based DIFF-rGFP assay system for generalized discovery of viral protease Inhibitors</strong> -
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Viral protease is an attractive target for antiviral therapeutics, but current viral protease inhibitor screening methods still need to be improved. Here, we systematically investigated the sites that may accommodate exogenous short peptides within Enhanced Green Fluorescent Protein (EGFP)and constructed a series of recombinant green fluorescent proteins (rGFPs). Meanwhile, a cell-based, simple and reliable assay system named DIFF-rGFP was developed relying on the co-expression of rGFP and the protease for protease inhibitor screening with the example of 3CLpro, in which the fluorescence intensity increases with the action of the inhibitor. The DIFF-rGFP assay avoided the requirement of a higher biosafety lab and can be performed in a high-throughput manner. For proof of concept, we demonstrated this method to discover novel inhibitors against SARS-CoV-2. We believe the proposed method, in combination with available drug libraries, may accelerate the identification of novel antivirals.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.01.577684v1" target="_blank">Development of a cell-based DIFF-rGFP assay system for generalized discovery of viral protease Inhibitors</a>
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<li><strong>OpenSAFELY: a platform for analysing electronic health records designed for reproducible research</strong> -
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<div>
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Electronic health records (EHRs) and other administrative health data are increasingly used in research to generate evidence on the effectiveness, safety, and utilisation of medical products and services, and to inform public health guidance and policy. Reproducibility is a fundamental step for research credibility and promotes trust in evidence generated from EHRs. At present, ensuring research using EHRs is reproducible can be challenging for researchers. Research software platforms can provide technical solutions to enhance the reproducibility of research conducted using EHRs. In response to the COVID-19 pandemic, we developed the secure, transparent, analytic open-source software platform OpenSAFELY designed with reproducible research in mind. OpenSAFELY mitigates common barriers to reproducible research by: standardising key workflows around data preparation; removing barriers to code-sharing in secure analysis environments; enforcing public sharing of programming code and codelists; ensuring the same computational environment is used everywhere; integrating new and existing tools that encourage and enable the use of reproducible working practices; and providing an audit trail for all code that is run against the real data to increase transparency. This paper describes OpenSAFELY’s reproducibility-by-design approach in detail.
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</div>
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://osf.io/hj2sg/" target="_blank">OpenSAFELY: a platform for analysing electronic health records designed for reproducible research</a>
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<li><strong>Recapitulating memory B cell responses in a Lymphoid Organ-Chip to evaluate mRNA vaccine boosting strategies</strong> -
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<div>
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Predicting the immunogenicity of candidate vaccines in humans remains a challenge. To address this issue, we developed a Lymphoid Organ-Chip (LO chip) model based on a microfluidic chip seeded with human PBMC at high density within a 3D collagen matrix. Perfusion of the SARS-CoV-2 Spike protein mimicked a vaccine boost by inducing a massive amplification of Spike-specific memory B cells, plasmablast differentiation, and Spike-specific antibody secretion. Features of lymphoid tissue, including the formation of activated CD4+ T cell/B cell clusters and the emigration of matured plasmablasts, were recapitulated in the LO chip. Importantly, myeloid cells were competent at capturing and expressing mRNA vectored by lipid nanoparticles, enabling the assessment of responses to mRNA vaccines. Comparison of on-chip responses to Wuhan monovalent and Wuhan/Omicron bivalent mRNA vaccine boosts showed equivalent induction of Omicron neutralizing antibodies, pointing at immune imprinting as reported in vivo. The LO chip thus represents a versatile platform suited to the preclinical evaluation of vaccine boosting strategies.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.02.02.578553v1" target="_blank">Recapitulating memory B cell responses in a Lymphoid Organ-Chip to evaluate mRNA vaccine boosting strategies</a>
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<li><strong>Stratification of viral shedding patterns in saliva of COVID-19 patients</strong> -
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<div>
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Living with COVID-19 requires continued vigilance against the spread and emergence of variants of concern (VOCs). Rapid and accurate saliva diagnostic testing, alongside basic public health responses, is a viable option contributing to effective transmission control. Nevertheless, our knowledge regarding the dynamics of SARS-CoV-2 infection in saliva is not as advanced as our understanding of the respiratory tract. Here we analyzed longitudinal viral load data of SARS-CoV-2 in saliva samples from 144 patients with mild COVID-19 (a combination of our collected data and published data). Using a mathematical model, we successfully stratified infection dynamics into three distinct groups with clear patterns of viral shedding: viral shedding durations in the three groups were 11.5 days (95% CI: 10.6 to 12.4), 17.4 days (16.6 to 18.2), and 30.0 days (28.1 to 31.8), respectively. Surprisingly, this stratified grouping remained unexplained despite our analysis of 47 types of clinical data, including basic demographic information, clinical symptoms, results of blood tests, and vital signs. Additionally, we quantified the expression levels of 92 micro-RNAs in a subset of saliva samples, but these also failed to explain the observed stratification, although the mir-1846 level may have been weakly correlated with peak viral load. Our study provides insights into SARS-CoV-2 infection dynamics in saliva, highlighting the challenges in predicting the duration of viral shedding without indicators that directly reflect an individual's immune response, such as antibody induction. Given the significant individual heterogeneity in the kinetics of saliva viral shedding, identifying biomarker(s) for viral shedding patterns will be crucial for improving public health interventions in the era of living with COVID-19.
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<div class="article-link article-html-link">
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2024.01.30.578034v1" target="_blank">Stratification of viral shedding patterns in saliva of COVID-19 patients</a>
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<li><strong>Adaptive Regularized Tri-Factor Non-Negative Matrix Factorization for Cell Type Deconvolution</strong> -
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<div>
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Motivation: Accurate deconvolution of cell types from bulk gene ex- pression is crucial for understanding cellular compositions and uncovering cell-type specific differential expression and physiological states of diseased tissues. Existing deconvolution methods have limitations, such as requiring complete cellular gene expression signatures or neglecting partial biological information. Moreover, these methods often overlook varying cell-type mRNA amounts, leading to biased proportion estimates. Additionally, they do not effectively utilize valuable reference information from external studies, such as means and ranges of population cell-type proportions. Results: To address these challenges, we introduce an Adaptive Regular- ized Tri-factor non-negative matrix factorization approach for deconvolution (ARTdeConv). We rigorously establish the numerical convergence of our algorithm. Through benchmark simulations, we demonstrate the superior per- formance of ARTdeConv compared to state-of-the-art reference-free methods. In a real-world application, our method accurately estimates cell proportions, as evidenced by the nearly perfect Pearson’s correlation between ARTdeConv estimates and flow cytometry measurements in a dataset from a trivalent influenza vaccine study. Moreover, our analysis of ARTdeConv estimates in COVID-19 patients reveals patterns consistent with important immunological phenomena observed in other studies. Availability and implementation: The proposed method, ARTdeConv, is implemented as an R package and can be accessed on GitHub for researchers and practitioners at https://github.com/gr8lawrence/ARTDeConv. Keywords: Cell-type deconvolution, Convergence analysis, Multiplicative update algorithm, Non-negative matrix factorization, RNA sequencing, Single cell data
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🖺 Full Text HTML: <a href="https://www.biorxiv.org/content/10.1101/2023.12.07.570631v2" target="_blank">Adaptive Regularized Tri-Factor Non-Negative Matrix Factorization for Cell Type Deconvolution</a>
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<h1 data-aos="fade-right" id="from-clinical-trials">From Clinical Trials</h1>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>SMILE: Clinical Trial to Evaluate Mindfulness as Intervention for Racial and Ethnic Populations During COVID-19</strong> - <b>Conditions</b>: Anxiety; COVID-19 Pandemic <br/><b>Interventions</b>: Behavioral: Mindfulness <br/><b>Sponsors</b>: University of North Carolina, Chapel Hill; National Institute on Minority Health and Health Disparities (NIMHD); RTI International <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study to Learn About a Combined COVID-19 and Influenza Shot in Healthy Adults</strong> - <b>Conditions</b>: Influenza, Human, SARS-CoV-2 Infection, COVID-19 <br/><b>Interventions</b>: Biological: BNT162b2 (Omi XBB.1.5)/RIV; Biological: BNT162b2 (Omi XBB.1.5); Biological: RIV; Other: Normal saline placebo <br/><b>Sponsors</b>: Pfizer <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Effects of Nutritional Intervention on Health Parameters in Participants With Type 2 Diabetes Mellitus</strong> - <b>Conditions</b>: Diabetes Mellitus Type 2; Diabetes Mellitus Type 2 in Obese; Diabetes; Diabetes Mellitus Non-insulin-dependent; Hypertension; Type 2 Diabetes Mellitus <br/><b>Interventions</b>: Behavioral: Nutritional Intervention <br/><b>Sponsors</b>: Sao Jose do Rio Preto Medical School; Fundação de Amparo à Pesquisa do Estado de São Paulo <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>The Impact of the Covid-19 Pandemic on Orthopedic Trauma Management</strong> - <b>Conditions</b>: Trauma; COVID-19 Pandemic <br/><b>Interventions</b>: Other: epidemyolojical <br/><b>Sponsors</b>: Bakirkoy Dr. Sadi Konuk Research and Training Hospital <br/><b>Completed</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Open-label, Multi-centre, Non-Inferiority Study of Safety and Immunogenicity of BIMERVAX for the Prevention of COVID-19 in Adolescents From 12 Years to Less Than 18 Years of Age.</strong> - <b>Conditions</b>: SARS CoV 2 Infection <br/><b>Interventions</b>: Biological: BIMERVAX <br/><b>Sponsors</b>: Hipra Scientific, S.L.U; Veristat, Inc.; VHIR; Asphalion <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>A Study of Amantadine for Cognitive Dysfunction in Patients With Long-Covid</strong> - <b>Conditions</b>: Long COVID; Post-Acute COVID-19 Syndrome <br/><b>Interventions</b>: Drug: Amantadine; Other: Physical, Occupational, Speech Therapy; Other: Provider Counseling; Other: Medications for symptoms management <br/><b>Sponsors</b>: University of Texas Southwestern Medical Center <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Study on the Effect of Incentive Spirometer-based Respiratory Training on the Long COVID-19</strong> - <b>Conditions</b>: COVID-19 Pandemic; Diabetes; Hypertension; Cardiac Disease; Long COVID <br/><b>Interventions</b>: Behavioral: Incentive Spirometer respiratory training <br/><b>Sponsors</b>: National Taipei University of Nursing and Health Sciences; Tri-Service General Hospital <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Balance Acceptance and Commitment Therapy for Long COVID</strong> - <b>Conditions</b>: Post-COVID-19 Syndrome; Long COVID <br/><b>Interventions</b>: Behavioral: Balance Acceptance and Commitment Therapy <br/><b>Sponsors</b>: King’s College London <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Predict + Protect Study: Exploring the Effectiveness of a Predictive Health Education Intervention on the Adoption of Protective Behaviors Related to ILI</strong> - <b>Conditions</b>: Influenza; Influenza A; Influenza B; COVID-19; Respiratory Syncytial Virus (RSV) <br/><b>Interventions</b>: Behavioral: ILI Predictive Alerts, Reactive Content, and Proactive Content; Behavioral: ILI Predictive Alerts, Reactive Content; Behavioral: Proactive Content; Behavioral: No Intervention <br/><b>Sponsors</b>: Evidation Health; Biomedical Advanced Research and Development Authority <br/><b>Not yet recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Long COVID-19 [11C]CPPC Study</strong> - <b>Conditions</b>: COVID Long-Haul <br/><b>Interventions</b>: Drug: [11C]CPPC Injection; Drug: [11C]CPPC Injection <br/><b>Sponsors</b>: Johns Hopkins University; Radiological Society of North America <br/><b>Recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Thrombohemorrhagic Complications of COVID-19</strong> - <b>Conditions</b>: COVID-19 (Coronavirus Disease 2019) <br/><b>Interventions</b>: Diagnostic Test: Prevention algorithm <br/><b>Sponsors</b>: Volgograd State Medical University <br/><b>Active, not recruiting</b></p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Combined Use of Immunoglobulin and Pulse Steroid Therapies in Severe Covid-19 Patients</strong> - <b>Conditions</b>: Pulse Steroid and Immunoglobulins Drugs in Covid 19 Patients <br/><b>Interventions</b>: Drug: pulse steroid and nanogam <br/><b>Sponsors</b>: Konya City Hospital <br/><b>Completed</b></p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-pubmed">From PubMed</h1>
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<ul>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Terpenes and cannabidiol against human corona and influenza viruses-Anti-inflammatory and antiviral in vitro evaluation</strong> - The activity of the terpenes and Cannabidiol (CBD) against human coronavirus (HCoV) strain OC43 and influenza A (H1N1) was evaluated in human lung fibroblasts (MRC-5 cells). Also, we examined whether these ingredients inhibit pro-inflammatory cytokines in peripheral blood mononuclear cells (PBMC). The tested preparations exhibited both anti-inflammatory and antiviral effects. The combination of terpenes was effective against both HCoV-OC43 and influenza A (H1N1) virus. The addition of CBD…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Plasma and urine proteomics and gut microbiota analysis reveal potential factors affecting COVID-19 vaccination response</strong> - The efficacy of COVID-19 vaccination relies on the induction of neutralizing antibodies, which can vary among vaccine recipients. In this study, we investigated the potential factors affecting the neutralizing antibody response by combining plasma and urine proteomics and gut microbiota analysis. We found that activation of the LXR/FXR pathway in plasma was associated with the production of ACE2-RBD-inhibiting antibodies, while urine proteins related to complement system, acute phase response…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Relative deficiency in interferon-γ-secreting CD4+ T cells is strongly associated with poorer COVID-19 vaccination responses in older adults</strong> - Although the two-dose mRNA vaccination regime provides protection against SARS-CoV-2, older adults have been shown to exhibit poorer vaccination responses. In addition, the role of vaccine-induced T-cell responses is not well characterised. We aim to assess the impact of age on immune responses after two doses of the BNT162b2 mRNA vaccine, focussing on antigen-specific T-cells. A prospective 3-month study was conducted on 15 young (median age 31 years, interquartile range (IQR) 25-35 years) and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Structural Basis for coronaviral main proteases Inhibition by a 3CL Protease Inhibitor- GC376</strong> - The main protease (M^(pro)) of coronaviruses participates in viral replication, serving as a hot target for drug design. GC376 is able to effectively inhibit the activity of M^(pro), which is due to nucleophilic addition of GC376 by binding covalently with Cys145 in M^(pro) active site. Here, we used fluorescence resonance energy transfer (FRET) to analyze the IC(50) values of GC376 against M^(pro)s from six different coronaviruses (SARS-CoV-2, HCoV-229E, HCoV-HUK1, MERS-CoV, SARS-CoV,…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>PCSK9 inhibition with orally administered NNC0385-0434 in hypercholesterolaemia: a randomised, double-blind, placebo-controlled and active-controlled phase 2 trial</strong> - BACKGROUND: Currently available injectable drugs that target proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce serum LDL cholesterol and improve cardiovascular outcomes. This phase 2 study assessed NNC0385-0434, an oral PCSK9 inhibitor, in individuals receiving oral lipid-lowering therapy.</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In vitro broad-spectrum antiviral activity of MIT-001, a mitochondria-targeted reactive oxygen species scavenger, against severe acute respiratory syndrome coronavirus 2 and multiple zoonotic viruses</strong> - The COVID-19 pandemic caused by SARS-CoV-2 becomes a serious threat to global health and requires the development of effective antiviral therapies. Current therapies that target viral proteins have limited efficacy with side effects. In this study, we investigated the antiviral activity of MIT-001, a small molecule reactive oxygen species (ROS) scavenger targeting mitochondria, against SARS-CoV-2 and other zoonotic viruses in vitro. The antiviral activity of MIT-001 was quantified by RT-qPCR and…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Exploration of the P1 residue in 3CL protease inhibitors leading to the discovery of a 2-tetrahydrofuran P1 replacement</strong> - The virally encoded 3C-like protease (3CL^(pro)) is a well-validated drug target for the inhibition of coronaviruses including Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Most inhibitors of 3CL^(pro) are peptidomimetic, with a γ-lactam in place of Gln at the P1 position of the pseudopeptide chain. An effort was pursued to identify a viable alternative to the γ-lactam P1 mimetic which would improve physicochemical properties while retaining affinity for the target. Discovery of…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>In-situ synthesized and induced vertical growth of cobalt vanadium layered double hydroxide on few-layered V<sub>2</sub>CT<sub>x</sub> MXene for high energy density supercapacitors</strong> - Two-dimensional (2D) MXene nanomaterials display great potential for green energy storage. However, as a result of self-stacking of MXene nanosheets and the presence of conventional binders, MXene-based nanomaterials are significantly hindered in their rate capability and cycling stability. We successfully constructed a self-supported stereo-structured composite (TMA-V(2)CT(x)/CoV-LDH/NF) by in-situ growing 2D cobalt vanadium layered double hydroxide (CoV-LDH) vertically on 2D few-layered…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Possible pharmacological targets and mechanisms of sivelestat in protecting acute lung injury</strong> - Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a life-threatening syndrome induced by various diseases, including COVID-19. In the progression of ALI/ARDS, activated neutrophils play a central role by releasing various inflammatory mediators, including elastase. Sivelestat is a selective and competitive inhibitor of neutrophil elastase. Although its protective effects on attenuating ALI/ARDS have been confirmed in several models of lung injury, clinical trials have presented…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Natural products from Streptomyces spp. as potential inhibitors of the major factors (holoRdRp and nsp13) for SARS-CoV-2 replication: an in silico approach</strong> - The COVID-19 pandemic caused unprecedented damage to humanity, and while vaccines have been developed, they are not fully effective against the SARS-CoV-2 virus. Limited targeted drugs, such as Remdesivir and Paxlovid, are available against the virus. Hence, there is an urgent need to explore and develop new drugs to combat COVID-19. This study focuses on exploring microbial natural products from soil-isolated bacteria Streptomyces sp. strain 196 and RI.24 as a potential source of new targeted…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>NSP6 inhibits the production of ACE2-containing exosomes to promote SARS-CoV-2 infectivity</strong> - The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has triggered a global pandemic, which severely endangers public health. Our and others’ works have shown that the angiotensin-converting enzyme 2 (ACE2)-containing exosomes (ACE2-exos) have superior antiviral efficacies, especially in response to emerging variants. However, the mechanisms of how the virus counteracts the host and regulates ACE2-exos remain unclear. Here, we identified that SARS-CoV-2 nonstructural…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Activity and inhibition of the SARS-CoV-2 Omicron nsp13 R392C variant using RNA duplex unwinding assays</strong> - SARS-CoV-2 nsp13 helicase is an essential enzyme for viral replication and a promising target for antiviral drug development. This study compares the double-stranded RNA (dsRNA) unwinding activity of nsp13 and the Omicron nsp13^(R392C) variant, which is predominant in currently circulating lineages. Using in vitro gel- and fluorescence-based assays, we found that both nsp13 and nsp13^(R392C) have dsRNA unwinding activity with equivalent kinetics. Furthermore, the R392C mutation had no effect on…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Phospho-eIF4E stimulation regulates coronavirus entry by selective expression of cell membrane-residential factors</strong> - The eukaryotic translation initiation factor eIF4E can regulate cellular translation via phosphorylation on serine 209. In a recent study, by two rounds of TMT relative quantitative proteomics, we found that phosphorylated eIF4E (p-eIF4E) favors the translation of selected mRNAs, and the encoded proteins are mainly involved in ECM-receptor, focal adhesion, and PI3K-Akt signaling. The current paper is focused on the relationship between p-eIF4E and the downstream host cell proteins, and their…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Comparative immunogenicity and neutralizing antibody responses post heterologous vaccination with CoronaVac (Sinovac) and Vaxzevria (AstraZeneca) in HIV-infected patients with varying CD4+ T lymphocyte counts</strong> - The immune response to heterologous coronavirus disease (COVID-19) vaccination in people living with HIV (PLWH) is still unclear. Herein, our prospective cohort study aimed to compare the immune response of heterologous vaccination with CoronaVac (Sinovac) and Vaxzevria (AstraZeneca) between PLWH having CD4 counts ≤ 200 cells/µL (low CD4+) and > 200 cells/µL (high CD4+). Anti-receptor-binding domain (RBD) immunoglobulin G (IgG) levels and the percentage inhibition of neutralizing antibodies…</p></li>
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<li data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><p data-aos="fade-left" data-aos-anchor-placement="bottom-bottom"><strong>Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial</strong> - Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual…</p></li>
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</ul>
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<h1 data-aos="fade-right" id="from-patent-search">From Patent Search</h1>
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